tbuckley/cabot-search huggingface dataset:
Virus-like particle vaccinology, from bench to bedside
Authors: Mona O. Mohsen, Martin F. Bachmann
Journal: Cellular and Molecular Immunology (2022)

Virus-like particles (VLPs) have become key tools in biology, medicine and even engineering. After their initial use to resolve viral structures at the atomic level, VLPs were rapidly harnessed to develop antiviral vaccines followed by their use as display platforms to generate any kind of vaccine. Most recently, VLPs have been employed as nanomachines to deliver pharmaceutically active products to specific sites and into specific cells in the body. Here, we focus on the use of VLPs for the development of vaccines with broad fields of indications ranging from classical vaccines against viruses to therapeutic vaccines against chronic inflammation, pain, allergy and cancer. In this review, we take a walk through time, starting with the latest developments in experimental preclinical VLP-based vaccines and ending with marketed vaccines, which earn billions of dollars every year, paving the way for the next wave of prophylactic and therapeutic vaccines already visible on the horizon.
Differential prognostic impact of cytopenic phenotype in prefibrotic vs overt primary myelofibrosis
Authors: Giacomo Coltro, Francesco Mannelli, Giuseppe Gaetano Loscocco, Carmela Mannarelli, Giada Rotunno, Chiara Maccari, Fabiana Pancani, Alessandro Atanasio, Alessandro Maria Vannucchi, Paola Guglielmelli
Journal: Blood Cancer Journal (2022)
Metagenomics combined with activity-based proteomics point to gut bacterial enzymes that reactivate mycophenolate
Authors: Joshua B. Simpson, Josh J. Sekela, Amanda L. Graboski, Valentina B. Borlandelli, Marissa M. Bivins, Natalie K. Barker, Alicia A. Sorgen, Angie L. Mordant, Rebecca L. Johnson, Aadra P. Bhatt, Anthony A. Fodor, Laura E. Herring, Hermen Overkleeft, John R. Lee, Matthew. R. Redinbo
Journal: Gut Microbes (2022)

Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and to treat autoimmune diseases. MMF usage, however, is limited by severe gastrointestinal toxicity that is observed in approximately 45% of MMF recipients. The active form of the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation by bacterial β-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within the gastrointestinal tract. GUS enzymes demonstrate distinct substrate preferences based on their structural features, and gut microbial GUS enzymes that reactivate MPA have not been identified. Here, we compare the fecal microbiomes of transplant recipients receiving MMF to healthy individuals using shotgun metagenomic sequencing. We find that neither microbial composition nor the presence of specific structural classes of GUS genes are sufficient to explain the differences in MPA reactivation measured between fecal samples from the two cohorts. We next employed a GUS-specific activity-based chemical probe and targeted metaproteomics to identify and quantify the GUS proteins present in the human fecal samples. The identification of specific GUS enzymes was improved by using the metagenomics data collected from the fecal samples. We found that the presence of GUS enzymes that bind the flavin mononucleotide (FMN) is significantly correlated with efficient MPA reactivation. Furthermore, structural analysis identified motifs unique to these FMN-binding GUS enzymes that provide molecular support for their ability to process this drug glucuronide. These results indicate that FMN-binding GUS enzymes may be responsible for reactivation of MPA and could be a driving force behind MPA-induced GI toxicity.
Myc inhibition tips the immune balance to promote antitumor immunity
Authors: Chao Yang, Yun Liu, Yudi Hu, Liang Fang, Zhe Huang, Huanhuan Cui, Jun Xie, Yazhen Hong, Wei Chen, Nengming Xiao, Qiyuan Li, Wen-Hsien Liu, Changchun Xiao
Journal: Cellular and Molecular Immunology (2022)
Interaction between dermal papilla cells and follicular epithelial cells in vitro: effect of androgen
Authors: S.I. AMI, S.K. RATA, T.S. NODA, S.T. KAYASU
Journal: British Journal of Dermatology (2006)

Summary To investigate the mode of action of testosterone on human hair follicles, we studied the localization of androgen receptors in hair follicles and cultured dermal papilla cells from different body sites, using immunohistochemistry with a polyclona) antibody. Androgen receptors were detected in the dermal papilla cells of beard and axillary hair follicles, but not in those of occipital scalp hair follicles. Epithelial cells of the hair follicles were not stained by the antibody. Androgen receptors were also detected in the nuclei of cultured beard and axillary dermal papilla cells, but the dermal papilla cells from occipital scalp hair follicles showed little staining with this antibody. We also examined the effects of testosterone on the DNA synthesis and proliferation of cultured outer root sheath cells and dermal papilla cells. Testosterone did not have a proliferative effect on either type of cell when cultured alone. In contrast, testosterone significantly stimulated the proliferation of outer root sheath cells which were co-cultured with beard or axillary dermal papilla cells, without cell contact. No such effect was observed when dermal papilla cells from occipital scalp hair follicles were used in the cultures. This proliferative effect of testosterone was concentration-dependent, and was antagonized by cyproterone acetate. Our findings suggest that dermal papilla cells from the beard and axillary hair follicles produce androgen-dependent diffusible growth factors which stimulate follicular epithelial cells.
The unique role of innate lymphoid cells in cancer and the hepatic microenvironment
Authors: Sophie Curio, Gabrielle T. Belz
Journal: Cellular and Molecular Immunology (2022)

Cancer is a complex disease, and despite incredible progress over the last decade, it remains the leading cause of death worldwide. Liver cancers, including hepatocellular carcinoma (HCC), and liver metastases are distinct from other cancers in that they typically emerge as a consequence of long-term low-grade inflammation. Understanding the mechanisms that underpin inflammation-driven tissue remodeling of the hepatic immune environment is likely to provide new insights into much needed treatments for this devastating disease. Group 1 innate lymphoid cells (ILCs), which include natural killer (NK) cells and ILC1s, are particularly enriched in the liver and thought to contribute to the pathogenesis of a number of liver diseases, including cancer. NK cells are an attractive, but underexplored, therapeutic target in hepatic disease due to their role in immunosurveillance and their ability to recognize and eliminate malignant cells. ILC1s are closely related to and share many phenotypic features with NK cells but are less well studied. Thus, their utility in immunotherapeutic approaches is not yet well understood. Here, we review our current understanding of ILCs in cancer with a particular focus on liver and liver-related diseases.
Pain measurement in painful skin conditions and rheumatoid arthritis randomized controlled trials: a scoping review to inform pain measurement in hidradenitis suppurativa
Authors: Samar B. Hasan, Riham Gendra, JaBreia James, Delyth Morris, Lauren A.V. Orenstein, John R. Ingram
Journal: British Journal of Dermatology (2022)

Abstract Background Pain is the most common and bothersome symptom experienced by people with hidradenitis suppurativa (HS) and has been prioritized as an outcome domain by the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Objectives To perform a scoping review of pain measurement in randomized control trials (RCTs) of painful skin conditions (PSCs) and use of the pain numerical rating scale (NRS) and visual analogue scale (VAS) in rheumatoid arthritis RCTs, to inform the efforts of HISTORIC to reach consensus on how to measure pain intensity in HS trials. Methods A search was conducted on several publication databases. Inclusion criteria were RCTs with a minimum of 10 participants that measured pain intensity. Results Pain NRS and VAS were used in 68% of PSC trials. Respectively, 77% and 87% of PSC and rheumatoid arthritis RCTs did not specify the recall window. The commonest recall window in PSCs when specified was 24 h. In total, 33% of PSC trials assessed maximum pain intensity and 3% average pain intensity, while 87% of rheumatoid arthritis trials did not provide details. Pain data were reported as mean difference by 76% of PSC trials and 75% of rheumatoid arthritis trials. Respectively, 10% and 11% of PSC and rheumatoid arthritis studies reported pain as the percentage of patients reaching a desirable state and only 1% and 2% reported number needed to treat. Conclusions While pain NRS and VAS are standard methods to measure pain intensity in PSCs, key details such as the recall window are often omitted and there is no consensus on how to report pain NRS data. What is already known about this topic? Pain is the most burdensome symptom experienced by patients with hidradenitis suppurativa and has been prioritized as an outcome domain by the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). What does this study add? Our review shows substantial variation in how pain numerical rating scale (NRS) and visual analogue scale are utilized in clinical trials. This variation restricts meta-analysis of pain intensity results.There is a need for consensus regarding the recall window for pain NRS and maximum vs. average pain, and whether current pain should be measured.
Current Medical literature.
Journal: JAMA (1901)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Acute Glomerulonephritis.
Authors: F REUBI
Journal: Annals of Internal Medicine (1968)

Background.Glomerular hypercellularity due to resident glomerular cell proliferation and leucocyte infiltration has been described in acute poststreptococcal glomerulonephritis (APSGN).APSGN usually resolves without progression.However, the mechanism of resolution remains to be determined.Methods.Renal biopsy tissues from 15 patients with APSGN (obtained 1-31 days after disease onset) and five control patients with minor glomerular abnormality were evaluated with respect to glomerular resolution.Apoptotic cells were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) as well as by immunostaining of single-stranded DNA (ssDNA).Results.The number of glomerular cells was high in the early-phase of APSGN and decreased over time.No TUNELþ glomerular cells were found in control subjects, whereas prominent glomerular TUNELþ cells were observed in APSGN patients, particularly in the early phase of the disease.The number of glomerular TUNELþ cells decreased exponentially but was still prominent in renal tissue biopsied at 31 days after disease onset.Double staining for ssDNA and glomerular cell markers showed that glomerular apoptotic cells were predominantly mesangium and endothelial cells, with some neutrophils and macrophages.Conclusions.These results suggest that apoptosis exists in the glomerulus in patients with APSGN from the early to the late stages of the disease and contributes to the resolution of glomerular hypercellularity.
Simvastatin-hydroxyapatite coatings prevent biofilm formation and improve bone formation in implant-associated infections
Authors: Tiantong Sun, Jie Huang, Wang Zhang, Xuanqi Zheng, Hong Wang, Jing Liu, Huijie Leng, Wanqiong Yuan, Chunli Song
Journal: Bioactive Materials (2022)

Implant-associated infections (IAIs) caused by biofilm formation are the most devastating complications of orthopedic surgery. Statins have been commonly and safely used drugs for hypercholesterolemia for many years. Here, we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated infections. The antibacterial properties of simvastatin against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro was confirmed by crystal violet staining and live-dead bacterial staining. We developed a simvastatin-and hydroxyapatite (Sim-HA)-coated titanium alloy via electrochemical deposition. Sim-HA coatings inhibited Staphylococcus aureus biofilm formation and improved the biocompatibility of the titanium alloy. Sim-HA coatings effectively prevented Staphylococcus aureus IAI in rat femurs, as confirmed by radiological assessment and histological examination. The antibacterial effects of the Sim-HA coatings were attributed to their inhibitory effects on biofilm formation, as verified by scanning electron microscopic observations and bacterial spread plate analysis. In addition, the Sim-HA coatings enhanced osteogenesis and osteointegration, as verified by micro-CT, histological evaluation, and biomechanical pull-out tests. In summary, Sim-HA coatings are promising implant materials for protection against biofilm-associated infections.
OP0079 SYNOVIAL FIBROBLASTS – T CELL INTERACTIONS ARE MAJOR DRIVERS OF INFLAMMATION: A CLOSER LOOK INTO THE JOINT
Authors: M. Kugler, M. Dellinger, F. Kartnig, A. Tosevska, L. Müller, T. Preglej, L. Heinz, H. Kiener, G. Steiner, D. Aletaha, T. M. Karonitsch, M. Bonelli
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid Arthritis (RA) is a chronic inflammatory disease, which is characterized by synovial inflammation resulting in bone and cartilage destruction. Crosstalk between activated fibroblast-like synoviocytes (FLS) and immune cells, such as CD4 + T cells, within the synovium might amplify synovial inflammation and joint destruction. Objectives To define the interaction profile of activated FLS and CD4 + T cells within an inflammatory setting and to elucidate its consequence on synovial inflammation. Methods To screen for factors that activate FLS in RA, isolated FLS were treated with different inflammatory cytokines and transcriptomic changes were measured with RNA-seq. Fluorescence activated cell sorting (FACS) purified naïve CD4 + T-cells from the same patients were co-cultured with the cytokine pre-treated FLS. Automated fluorescence microscopy and downstream bioinformatic image analysis allowed visualization and quantification of cell-cell interactions. After co-culture T-cells were isolated and T-cell activation, proliferation and differentiation was determined by flow cytometry. Results To model the in vivo situation, FLS were pre-stimulated with different pro- and anti-inflammatory cytokines. RNA-seq revealed cytokine specific activation patterns of FLS. Correspondingly, we observed distinct CD4 + T cells – FLS interaction profiles depending on the cytokine used for FLS activation. In line with distinct interaction profiles, specific patterns in CD4 + T cells activation, proliferation and differentiation of naïve T cells into CD62L high CD45RO high memory T cells could be detected. Signatures of cytokine-stimulated FLS could be identified in transcriptomic data from synovial tissue samples. Conclusion Within this study, we describe how cytokine induced CD4 + T cells – FLS interactions impact on T-cell proliferation, activation and differentiation. References [1]Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019. [2]Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001. [3]Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. The Lancet. 2016;388(10055):2023-38. [4]Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233-55. [5]Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019. Disclosure of Interests None declared.
OP0046 EVALUATION OF THE EFFICACY OF TOPICALLY APPLIED TACROLIMUS IN THE TREATMENT OF ORAL ULCERS IN BEHCET’S DISEASE: A DOUBLE BLIND PLACEBO CONTROLLED STUDY
Authors: M. Hassanien, A. Moshrif, M. Galal, F. Abuzaid, D. Fathalla, E. Talaat
Journal: Annals of the Rheumatic Diseases (2022)

Background Treatment of Behcet disease (BD) associating oral ulcers is still challenging despite the advances in the systemic treatment modalities. Objectives We aimed to evaluate the clinical efficacy of topical Tacrolimus for treatment of BD. Methods In this double blind placebo controlled trial, forty BD patients with persistent active oral ulceration were equally randomized into group I (20 patients received oral colchicine plus topically applied tacrolimus) and group II (20 patients received oral colchicine plus placebo oral gel). All participants were evaluated based on Behcet’s Disease Current Activity Form (BDCAF), Ulcer Severity Score (USS) and visual analog scale (VAS) before treatment, and at four-time points post-treatment (15 days, 1 st , 2 nd, and 3rd months). Results VAS was significantly lower in group I after 2 weeks (p= 0.037) and 3 months (0.025) than in group II. USS was significantly lower in group I after 3 months of follow up regarding the number of ulcers (p=0.014), ulcer size (p=0.022), and duration (p=0.009). BDCAF showed significant improvement in 3 months follow up within each group (p&lt;0.001 for both groups), while there was insignificant difference between both groups(p=0.347). Conclusion Topical Tacrolimus has been proven to be a safe and effective adjunctive therapy in the management of oral ulcerations in BD. Disclosure of Interests Manal Hassanien: None declared, Abdelhfeez Moshrif Speakers bureau: Amgen, Jansen, Novartis, Mostafa Galal: None declared, Fathy Abuzaid: None declared, Dian Fathalla: None declared, Esraa Talaat: None declared.
OP0114 IDENTIFICATION AND FUNCTIONAL PREDICTION OF LONG NONCODING RNA RELATED TO CONNECTIVE TISSUE DISEASE-ASSOCIATED INTERSTITIAL LUNG DISEASES
Authors: F. Dai, Q. B. Zhang, Y. X. He, Y. P. Tang, T. Y. Lei, Y. Jiang, Y. F. Qing
Journal: Annals of the Rheumatic Diseases (2022)

Background Recently, the role of long noncoding RNA (lncRNA) in rheumatic immune diseases has attracted widespread attention 1 . However, knowledge of lncRNA in connective tissue disease-associated interstitial lung disease (CTD-ILD) is limited. Objectives To explore the expression profile of lncRNA in peripheral blood mononuclear cells (PBMCs) of CTD-ILD patients and the possible mechanisms of significantly differentially expressed lncRNA involved in CTD-ILD, especially systemic sclerosis (SSc)-ILD and rheumatoid arthritis (RA)-ILD. Methods LncRNA microarray analysis was used to identify the pattern of lncRNA dysregulation between CTD-ILD and connective tissue disease without associated interstitial lung disease (CTD-NILD). Differential genes were identified by bioinformatic analysis. Relative expression levels of five differentially expressed lncRNAs in 120 SSc and RA patients with or without ILD were detected by quantitative reverse-transcription PCR (qRT-PCR). Results The differential gene expression analysis revealed 46 lncRNAs were upregulated while 194 lncRNAs were downregulated in the CTD-ILD group compared to the CTD-NILD group (Figure 1). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified several significant biological processes and signaling pathways, including NF-kappa B signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway, B cell receptor signaling pathway. QRT-PCR confirmed that the selected target genes were differentially expressed in different groups. In particular, the ENST00000604692 expression level was significantly higher in the ILD than the NILD group (p&lt;0.05, Figure 1); T311354 and arginase-1were significantly higher in SSc than RA group; Furthermore, the area under receiver operating characteristic curve for ENST00000604692 in predicting ILD from NILD was 0.797 (Figure 1). Conclusion This research has demonstrated, for the first time, the specific profile of lncRNA in PBMCs of CTD-ILD patients and the potential signal pathways related to the pathogenesis of CTD-ILD. ENST00000604692 can effectively distinguish ILD group from NILD group,which may be a diagnostic indicator of CTD-ILD, especially SSc-ILD and RA-ILD. References [1]Guo CJ, Xu G, Chen LL. Mechanisms of Long Noncoding RNA Nuclear Retention. Trends Biochem Sci (2020) 45(11):947-60. doi: 10.1016/j.tibs.2020.07.001. Disclosure of Interests None declared